The objective of the biophysical nuclear magnetic resonance (NMR) program is the elucidation of the mechanisms by which chemicals and heavy metals present in the environment produce toxic effects in living systems. The use of NMR methodology in achieving this objective may be considered to fall into two broad categories: 1) In vivo metabolic analysis using NMR spectroscopy. Such studies probe the metabolism of chemicals and heavy metals in various tissues and organs directly when sufficient concentrations are present to permit detection. Additionally, studies of the effects of these agents on intermediary metabolism, the metabolism of high energy phosphate compounds, and on the pyridine nucleotide reduction charges are carried out when the levels of chemicals/heavy metals are well below the direct detection threshold, but can still lead to a toxic response as reflected in perturbations of those parameters. 2) In vitro studies of molecular structure and dynamics using NMR spectroscopy. Such studies are aimed both at obtaining a more complete understanding of the solution structure of chemical toxins, and toward the analysis of the mode of interaction of various toxic substances with presumed or demonstrated biological targets (e.g., nucleic acids, enzymes, etc.). As a consequence of the need to use specific labeling (including carbon-13 and fluorine-19 labeling) in connection with many of these NMR studies, the program includes a synthetic component, the goals of which are closely interfaced with the needs of the program. Finally, it is noted that an overriding motivation for this program is the evaluation and demonstration of the extent to which non-invasive analysis by NMR can be used to follow the progress of a toxic response in real time and with individual experimental animals, thereby leading to more efficient use of these animals in toxicity studies.